Larson, Henry

Abstract Introduction Since FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), there has been significant debate as to its role and comparable efficacy in relation to surgical therapies. We therefore sought to compare key outcomes between the two therapies. Objective To compare the satisfaction and adverse event profiles between surgery and CCH injections for the treatment of PD. Methods A randomized, controlled trial is ongoing. Participants were randomized 1:1 to receive either CCH + traction (RestoreX) + sildenafil (CCH) or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD (Surgery). Objective, standardized, and non-standardized assessments were obtained at baseline and 3, 6, 12, 24, 36, 48, and 60 months post-treatment. Key outcomes included differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Results A total of 40 men were randomized with 24-month data available in 29. Mean age was 54.7 years, PD duration 37.4 months (mo), composite curvature 73.1 degrees (deg), and penile length 12.7 cm. All baseline variables were similar between cohorts. Regarding primary outcomes, at 24-months post-treatment, CCH men were more likely to report being very satisfied with treatment (62% vs 25%, p < 0.05). For secondary outcomes, only questionnaire data were captured at two years without objective measurements obtained. No differences were noted between groups regarding subscales of the IIEF, PDQ, Beck’s Depression Inventory, or SEP-2, however CCH men had better SEP-3 positive responses (62% vs 19%, p = 0.02), indicating improved ability to maintain erections sufficient for intercourse. Surgery men reported higher subjective rates of length loss compared to CCH (81% vs 15%, p < 0.001) and curvature recurrence (56% vs 8%, p < 0.01), but similar rates with changes in sensation, indentation/hourglass, and erectile function. Both groups indicated similar willingness to undergo the therapy again. Interestingly, at 2-years, the majority of men in the Surgery arm said that their initial preference for treatment was surgery (56%), which decreased from a peak 86% at 1-year. However, in reviewing baseline information, 72% of Surgery men actually preferred CCH at study onset, highlighting a significant recall bias towards whatever treatment one actually ended up receiving. Conclusions Preliminary data suggests that when compared to surgery at 24-months, CCH men were more likely to be very satisfied with therapy, have greater subjective length improvements and lower curvature recurrence rates. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: PathRight Medical.

Abstract Introduction Limited data are available on the efficacy of collagenase clostridium histolyticum (CCH) on Peyronie’s disease (PD) in men with ventral curvatures. Our team previously published a limited series of outcomes of 25 men with ventral curvatures who underwent CCH. Given the paucity of data available, we sought to provide an updated series of outcomes in this important cohort. Objective To report outcomes of men undergoing CCH injections for PD based on initial direction of curvature, including absolute and percent improvement in curvature, adverse events (AE), and other subjective outcomes. Methods A prospective registry has been maintained of all men undergoing CCH injections since 2014. All men underwent curvature assessments and subjective questioning at the time of initial evaluation and prior to each subsequent series of injections. The method of injection and subsequent protocol have changed in a stepwise fashion since 2014 and currently include injecting 0.9 mg (diluted to 0.8 mL) on back-to-back days, injecting into the point of max curve with an erection on day 1, performing in-office modeling on day 2, utilizing Restorex traction beginning on day 2, and wrapping for 4-8 days depending on results. To review outcomes, clinicopathologic data were abstracted from the registry including relevant history, exam, and data obtained at the time of penile ultrasound and curvature assessment. Outcomes are reported using a “Most Recent” definition (most recent data point used, regardless if the patient continues or finished treatment) and “Completed 8 or Satisfied” (only included if the patient indicated that they were done with treatment or had finished the full 8 injections). Results A total of 560 patients (mean age 57 years) were identified from March 2014 through Feb 2023 and comprise our study cohort. Overall, 85 men had a ventral component to their curvature and 475 non-ventral. Baseline demographics and clinical factors were similar between groups, with the exception of penile length (ventral 14.0 cm, non-ventral 12.0 cm, p<0.0001), Psych and Physical subdomain of the Peyronie’s Disease Questionnaire (10 vs 12, p=0.03), and prior treatment with CCH (3% vs 16%, p=0.03). Following treatment, men in the ventral cohort exhibited possibly greater improvements in curvature (Most Recent Definition: -25 degrees vs -24, p=0.08; 45% vs 34%, p=0.03; Completed 8 or Satisfied Definition: -35 vs -25, p<0.05, 48% vs 38%, p=0.11). However, all other outcomes were similar between cohorts, including differences in subdomains of the IIEF and PDQ, use of traction therapy, and adverse events including ecchymoses, hematomas, and popping sensations. Importantly, no urethral complications were experienced in the ventral group. Conclusions Men with ventral PD may be effectively treated with CCH with similar AEs compared to other directions. Ventral curvatures are likely associated with greater overall curvature improvements compared to other directions. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo - Matt Ziegelmann.

Abstract Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), there has been significant debate as to its role and comparable efficacy in relation to surgical therapies. We have previously published results comparing the two therapies at 3-months post-treatment. Objective To compare various objective and subjective outcome measures at 12-months post-treatment between men undergoing CCH or surgery for PD. Methods A randomized, controlled trial (NCT04786106) is ongoing. Participants were randomized 1:1 to receive either CCH + traction (RestoreX) + sildenafil or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD. Objective, standardized (International Index of Erectile Function [IIEF] and Peyronie’s Disease Questionnaire [PDQ]), and non-standardized assessments were obtained at baseline, and post-treatment at 3, 6, 12, 24, 36, 48, and 60 months. Key outcomes included differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Curvature was measured in two planes and summed to provide a composite curvature. Penile length was measured from pubic symphysis to corona. All adjunctive therapies were stopped at 3-months post treatment completion (i.e., traction and sildenafil). Results A total of 40 men were randomized, with 38 completing treatment and 12-month data available on 28 men (CCH=12, surgery=16). Mean age at enrollment was 54.7 years, PD duration 37.4 months (mo), composite curvature 73.1 degrees (deg), and penile length 12.7 cm. All baseline variables were statistically similar between cohorts. Regarding primary outcomes, at 12-months post-treatment, CCH men reported being very satisfied 36%, satisfied 27%, and neutral 36% with none dissatisfied. Men in the Surgery cohort reported 14% very satisfied, 64% satisfied, 0% neutral, and 21% dissatisfied (p<0.01). For secondary outcomes, the median differences between CCH and Surgery were: IIEF-EFD (+2.0 vs +2.0, p=0.82), PDQ-physical (-5 vs -5, p=0.77, note, lower is better for PDQ scales), PDQ-pain (-1 vs 0, p=0.92), PDQ-bother (-7 vs -3, p=0.12), length change (+1.0 vs -0.13 cm, p<0.05), curvature absolute change (-37.5 vs -53.8 degrees, p=0.17), and curvature % improvement (55% vs 82%, p=0.15). Compared to 3-month data, Surgery men experienced greater curve recurrence (objective: Surgery +5 degrees vs -5 degrees CCH, p<0.05), decreased subjective penile length 62% vs 9% CCH (p<0.01) and decreased sensitivity (54% vs 27% CCH, p<0.05). Both groups reported similar rates of improved sexual function (CCH 82% vs 64%, p=0.30) and change in erectile function (CCH 55% improved, 9% worsened; Surgery 62% improved, 8% worsened, p=0.53). Both groups were also equally satisfied with their curvature (CCH 55% vs Surgery 54%, p=0.97), despite greater overall curve improvements in the Surgery arm. 75% of CCH men reported improved indentation/hourglass vs 56% Surgery, p<0.05. Both groups reported similar rates of being willing to do their treatment again (CCH 73% vs 77%, p=0.64), while 91% of CCH men would recommend it to a friend vs 77% Surgery (p=0.35). Conclusions Preliminary data suggests that when compared to surgery at 12-months, CCH men were more likely to be very satisfied, experience penile length increases, and less likely to experience dissatisfaction, curvature recurrence, and decreased penile sensation. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Matthew Ziegelmann - Endo Pharmaceuticals.

Abstract Background The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie’s disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. Aim The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. Methods Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. Outcomes Changes in penile curvature, Peyronie’s Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. Results A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was −25.0° in the ventral cohort vs −24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was −35.0° in the ventral cohort vs −25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie’s Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. Clinical Implications Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. Strengths and Limitations Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. Conclusion CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.